Biofilm-<i>i</i>: A Platform for Predicting Biofilm Inhibitors Using Quantitative Structure—Relationship (QSAR) Based Regression Models to Curb Antibiotic Resistance

Abstract

Antibiotic drug resistance has emerged as a major public health threat globally. One of the leading causes of drug resistance is the colonization of microorganisms in biofilm mode. Hence, there is an urgent need to design novel and highly effective biofilm inhibitors that can work either synergistically with antibiotics or individually. Therefore, we have developed a recursive regression-based platform “Biofilm-i” employing a quantitative structure–activity relationship approach for making generalized predictions, along with group and species-specific predictions of biofilm inhibition efficiency of chemical(s). The platform encompasses eight predictors, three analysis tools, and data visualization modules. The experimentally validated biofilm inhibitors for model development were retrieved from the “aBiofilm” resource and processed using a 10-fold cross-validation approach using the support vector machine and andom forest machine learning techniques. The data was further sub-divided into training/testing and independent validation sets. From training/testing data sets the Pearson’s correlation coefficient of overall chemicals, Gram-positive bacteria, Gram-negative bacteria, fungus, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Escherichia coli was 0.60, 0.77, 0.62, 0.77, 0.73, 0.83, 0.70, and 0.71 respectively via Support Vector Machine. Further, all the QSAR models performed equally well on independent validation data sets. Additionally, we also checked the performance of the random forest machine learning technique for the above datasets. The integrated analysis tools can convert the chemical structure into different formats, search for a similar chemical in the aBiofilm database and design the analogs. Moreover, the data visualization modules check the distribution of experimentally validated biofilm inhibitors according to their common scaffolds. The Biofilm-i platform would be of immense help to researchers engaged in designing highly efficacious biofilm inhibitors for tackling the menace of antibiotic drug resistance.

Keywords

• antibiotic drug resistance
• biofilm
• inhibitors
• chemical descriptors
• QSAR
• predictor